The proposed NIH U54 SCCPRIR at the University of California, San Francisco, is comprised of an integrated group of investigators working on the central theme of early development as it relates to the origins and biological consequences of human infertility. The objectives of the Center are: (a) discovery of mechanisms underlying early human development that are relevant to infertility and have the potential to translate into novel diagnostics and therapies for affected patients;(b) to train future leaders in reproductive biology and medicine research, with an emphasis on infertility;and (c) to participate in the NIH SCCPRIR Program, contributing to the science as well as to the training and mentoring of the next generation of reproductive/infertility researchers. The Center is comprised of three interactive projects, two pilot projects, and four cores with a focus on early development, from germ cell biogenesis and maturation to implantation and placentation, and is founded firmly in the disciplines of genetics, stem cell biology, reproductive biology, molecular and cell biology, and computational biology. Project I (Reijo Pera) investigates germ cell differentiation from human embryonic stem cells;Project II (Fisher) focuses on placentation and human trophoblast differentiation and notch signaling;Project III (Giudice) extends development to decidua-trophoblast interactions;Pilot I (Rinaudo) investigates trophoblast differentiation in in vivo and in vitro fertilized embryos;and Pilot II (Blelloch) investigates post-transcriptional regulation of trophoblast differentiation. These highly integrated projects are supported by four cores: Administrative, Cell Derivation and Isolation, Bioinformatics/Biostatistics, and Training/Mentoring/Advocacy. Strong, interactive clinical programs and clinical, basic, and translational training programs in reproductive biology, genetics, developmental biology, stem cell biology and medicine at UCSF contribute greatly to our Center, which is enriched by the UCSF environment of seminars, courses, and core facilities that foster stimulating exchanges among investigators and trainees. Our proposed Center has direct relevance to clinical translation, as infertility and its treatments are commonplace and carry significant long-term risks for the health of affected adults and their children. Our Center is designed to discover mechanisms underlying early human development and abnormalities in gametogenesis, implantation, and placentation that lead to infertility, miscarriage and poor pregnancy outcome - important goals to improve the public health.